A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration

Nat Rev Neurosci. 2016 Apr;17(4):251-60. doi: 10.1038/nrn.2016.13.


There has been an explosion in the number of papers discussing the hypothesis of 'pathogenic spread' in neurodegenerative disease - the idea that abnormal forms of disease-associated proteins, such as tau or α-synuclein, physically move from neuron to neuron to induce disease progression. However, whether inter-neuronal spread of protein aggregates actually occurs in humans and, if so, whether it causes symptom onset remain uncertain. Even if pathogenic spread is proven in humans, it is unclear how much this would alter the specific therapeutic approaches that are in development. A critical appraisal of this increasingly popular hypothesis thus seems both important and timely.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Neurodegenerative Diseases / complications
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology*
  • Neurons / pathology*
  • Protein Aggregation, Pathological / etiology*
  • Protein Transport
  • alpha-Synuclein / metabolism
  • tau Proteins / metabolism


  • alpha-Synuclein
  • tau Proteins